Acute Inflammation Flashcards
What is inflammation?
Inflammation is a defensive reaction (innate immune response) of a macro-organism against injury caused by trauma, toxic chemicals, or an invading pathogen
Protective response, but also a potentially harmful process- components of inflammation that are capable of destroying microbes can also injure bystander normal tissue
Rapid response to tissue injury; minutes/hours to develop and of relative short duration (hours or days)
What are the triggers of acute inflammation?
Triggers of acute inflammation
1. Infections:
Bacteria, viruses, parasites, fungi, toxins
2. Tissue damage due to:
Physical agents- frost bites, burns, radiation (ionising, UV)
Chemical agents- chemical burns, irritants, bites
Mechanical injury and ischemia- trauma, tissue crush, reduced blood flow
3. Foreign bodies:
Splinters, sutures, dirt
What purpose does acute inflammation serve?
Alert the body and initiate appropriate immune response
Limit spread (of infection and/or injury)
Protect injured site from becoming infected
Eliminate dead cells/ tissues
Create the conditions required for healing
Acute inflammation is a beneficial response
What are the signs of acute inflammation?
Heat- increased blood flow and metabolic activity
Redness- increased blood flow to injured area
Swelling- fluid accumulation due to permeability of vessels
Pain- release of pain mediators; pressure on nerve ends
Loss of function- damage
What are the components of an acute inflammatory response?
Vascular- acute changes in local vasculature
Vasodilation, plasma exudation and oedema
Cellular- infiltration of inflammatory cells
Cell recruitment, phagocytosis, NETosis
Humoral- release of inflammatory mediators
Complement, plasma factors, clotting cascade, cytokines and chemokines
Resolution- Inflammation is controlled and self-limiting
Healing, regeneration and repair of tissue
What vascular events occur during acute inflammation?
Vasodilation: an increase in vascular diameter
Induced by histamine and serotonin released by injured cells, mast cells and macrophages
This results in hyperaemia (increase in blood volume to the area) (redness)
The increased blood volume heats up the tissues (heat)
Increased vascular permeability (micro vessels):
Leading to leakage of fluid into the tissues (swelling)
As exudate accumulates, pressure increases
Nerve endings are stimulated by the excess fluid and inflammatory mediators (pain)
Endothelial cell activation increasing their expression of adhesion molecules to stop and migrate onto the site of injury
Overall effect: leucocytes and plasma proteins exit vessels and enter the inflammation site to deal with infection
What is exudate?
Inflammatory exudate (due to increased vessel permeability) Water, salts, small plasma proteins (fibrinogen), inflammatory cells, red blood cells => get out of vessels and enter tissues or serous cavities Transudate= fluid leaks due to altered osmotic/hydrostatic pressure; vessel permeability normal
What are the different types of inflammatory exudate?
Serous:
A few cells, no/few microbes
Fluid derived from plasma/secreted by mesothelial cells
Serous cavities (pleura, peritoneum, pericardium)
Skin blisters (burns, viral infections
Purulent (fibrino-purulent)
Pus: many leucocytes (neutrophils), dead cells, microbes
Pus-producing bacteria (pyogenic) e.g. Staphylococci
E.g. acute appendicitis
E.g. abscess (localised collection of purulent inflammation)
Fibrinous
Fibrin deposition (derived from fibrinogen in plasma)
Result of large vascular leaks (fibrinogen exits blood and enters tissue)
Serous cavities (meninges, pleura, pericardium)
Can lead to scarring is not cleared (fibroblast => collagen)
Haemorrhagic
Red blood cells predominate
Due to blood vessel rupture, trauma
What are the steps leading to neutrophil recruitment?
Multistep process
1. Margination and rolling 2. Integrin activation by chemokines 3. Firm adhesion to endothelium 4. Transmigration through endothelium into tissue 5. Chemotaxis (attraction and movement) to inflamed site
What are selectins (what do they do)?
Mediate rolling of neutrophils
Expressed by activated endothelium
P-selectins- pre-formed granules
E-selectin- induced by IL-1 and TNF-a (cytokines produced by macrophages, mast cells, endothelial cells at site of inflammation)
Leucocytes (neutrophils, monocytes, lymphocytes) express L-selectins; ligands on endothelium
Endothelial selectins bind to ligands on neutrophils
Ligands-carbohydrates
Low-affinity interaction requiring repetitive contacts
How are integrins activated by chemokines?
Neutrophils rolling slows them down increasing contact to endothelium
Neutrophils express integrins
Integrins in low affinity configuration; no binding to ligands
Activated endothelial cells produce chemokines
Chemokines bind to receptors on neutrophils
Integrins are activated to change to high affinity configuration
Integrins are activated to change to high affinity configuration
Integrins bind to ligands on endothelium
Integrin ligands: ICAM-1, VCAM-1
Integrin ligands are induced by IL-1 and TNF-a (cytokines produced by macrophages, mast cells, endothelial cells at site of inflammation)
Results in firm adhesion of neutrophils to endothelium
What is neutrophil transmigration?
Neutrophils migrate through inter-endothelial spaces
Neutrophils pass through vessel wall and enter tissue
Migrate (chemotaxis) through tissue towards inflamed site
Gradient of chemoattractants guides migration in tissues
What is neutrophil chemotaxis?
Neutrophils migrate through inter-endothelial spaces
Neutrophils pass through vessel wall and enter tissue
Migrate (chemotaxis) through tissue towards inflamed site
Gradient of chemoattractants guides migration in tissues
How do neutrophils destroy?
Mechanisms involved:
Release of granule content
Phagocytosis
Generation of reactive oxygen/nitrogen species
Formation of Neutrophil Extracellular Traps (NETs) (netosis)
What are Neutrophil Extracellular Traps- NETs
Mesh of nuclear content (chromatin)
Mesh traps microbes
Contains anti-microbial molecules
